Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clingen PTEN Variant Curation Expert Panel, |
RCV004555635 | SCV005044852 | likely pathogenic | PTEN hamartoma tumor syndrome | 2024-02-09 | reviewed by expert panel | curation | NM_000314.8(PTEN):c.198G>T (p.Lys66Asn) meets criteria to be classified as likely pathogenic for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (ACMG Classification Rules Specified for PTEN Variant Curation version 3.0.0). Please see a summary of the rules and criteria codes in the "PTEN ACMG Specifications Summary" document (assertion method column). PS2: De novo (both maternity and paternity confirmed) observation in a patient with the disease and no family history. (internal laboratory contributor: SCV002526496.2) PS4_M: Probands with phenotype specificity score of 2-3.5. (internal laboratory contributor: SCV002526496.2) PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease. PP3: REVEL score > 0.7 (score of this variant=0.791) PM2_P: Absent in large sequenced populations (gnomAD). BS3_P: Functional studies showing no damaging effect on protein function. Score of this variant = 0.045 (>0, WT-like range) on high throughput phosphatase assay (PMID:29706350). Using the Bayesian point system (PMID: 29300386) for this variant with conflicting evidence: 1 benign supporting, 1 pathogenic strong, 1 pathogenic moderate and 3 pathogenic supporting codes get -1 + 4 + 2 + (1*3) points; total is 8 (Likely Pathogenic). |
| Gene |
RCV002255743 | SCV002526496 | pathogenic | not provided | 2022-06-15 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies suggest lipid phosphatase activity similar to wildtype but impaired protein stability (Mighell et al., 2018; Matreyek et al., 2018); This variant is associated with the following publications: (PMID: 12112531, 14655756, 29706350, 29785012, 19457929) |
| Institute of Human Genetics, |
RCV003128440 | SCV003804895 | uncertain significance | See cases | 2022-11-09 | criteria provided, single submitter | clinical testing | ACMG categories: PM2,PP1,PP5,BP1 |